Describe the reaction catalysed by pyruvate dehydrogenase for the conversion of pyruvate to acetyl CoA In the MITOCHONDRIAL MATRIX
This reaction describes one of the fates of pyruvate (the other being conversion into lactate). In this case, in a cell which contains a mitochondrion (all cells except erythrocytes) and sufficient levels of oxygen (usually all cells except muscle cells under extreme conditions) the pyruvate will be completely oxidised: so it will be fully converted into carbon dioxide and water.
The main way that ATP is continuously formed in a cell is through a cycle, in this case the TCA cycle, but to get there, pyruvate needs to first be converted into acetyl CoA. (this is not the only fate of acetyl CoA)
Pyruvate CH3COCOO- + CoA + NAD+ → acetylCoA CH3COCoA + CO2 + NADH + H+
The enzyme for this reaction is PYRUVATE DEHYDROGENASE – this enzyme needs thiamine – VITAMIN B1
Outline the metabolic events of the TCA cycle that result in the conversion of acetyl CoA into two molecules of CO2
STILL IN THE MITOCHONDRIAL MATRIX HERE.
The TCA cycle combines acetyl CoA with OXALOACETATE to form citrate, which then undergoes oxidations which release CO2, reduce 3NADH+H+ and one FADH2 and produce one GTP.
(there are two enzymes in this cycle: succinate dehydrogenase and fumerate hydratase which are oncosupressor genes, because their malfunctioning causes succinate and fumerate to build up in the cytosol and promote a pseudo-hypoxic condition which favours tumour development.
Also important here: the difference between FADH2 and NADH+H+
To become reduced: FAD accepts 2H+ and 2e-, while NAD+ accepts H+ and 2e-
Emphasise the role of the dehydrogenase enzymes in producing the reduced cofactors NADH+H+ and FADH2
DEHYDROGENASES REDUCE NADH+H+ AND FADH2
Describe the chemical nature and sequential arrangement of the electron carriers in the mitochondrial inner membrane
IN THE MITOCHONDRIAL MATRIX, INNER MEMBRANE AND INTER-MEMBRANOUS SPACE
The ETC is the main way that aerobic metabolism produces a lot of ATP. This is done through using the reduced NADH+H+ and FADH2.
So, we have electrons and protons we need to get rid of.
We need to oxidise NADH+H+ and FADH2.
This is the function of the ETC. To oxidise something, you need to reduce something else. What is reduced in this case? Iron. It goes from the ferrous Fe3+ state into the ferric Fe2+ state. Then it becomes oxidised, reducing the following iron molecule, until oxygen is reached. OXYGEN IS THE FINAL ELECTRON ACCEPTOR IN AEROBIC METABOLISM. It is the combination of oxygen with the electrons and hydrogens we have been removing from these organic molecules in glycolysis, the link reaction and krebs cycle that forms water and ends catabolism and energy production.
So how is this done?
There are CYTOCHROMES on the inner mitochondrial membrane. They are:
NADH-coenzyme Q reductase complex
Cytochrome C reductase complex
Cytochrome C oxidase complex (the final electron acceptor)
What happens is that:
Electrons are passed on from NADH+H+ and FADH2 onto the first cytochrome complex. For each TWO ELECTRONS, FOUR HYDROGENS are pumped into the intermembranous space
The electrons are passed onto the cytochrome C reductase complex, and the same thing is done, FOUR HYDROGENS are pumped into the intermembranous space
The same thing happens on the cytochrome C oxidase complex, and oxygen finally gets FOUR ELECTRONS and four hydrogens to form TWO water molecules.
The H+ protons then pass down their concentration gradient, from the intermembranous space into the mitochondrial matrix, spinning an ATP synthase protein, forming an ATP for each H+ that passes through.
Overall, about 30ATP are formed by all reactions.
Indicate how the electron carriers are organised in ‘complexes’ that conserve the energy from the reoxidation of NADH+H+ and FADH2 by pumping protons across the membrane, to create a proton and an electrochemical gradient
Done above :)